The Section works on the interaction of (complex) carbohydrate determinants with monoclonal antibodies (MAbs). The elucidation of this interaction - in great molecular detail - is important since it pertains to all ligand- protein interactions. Thus, drug-receptor, effector-receptor as well as viral-receptor interactions may be clarified. We are executing: 1. Physico-chemical studies on antibody/antigen systems. 2. The synthesis of ligands for affinity studies. 3. The manipulation of immunoglobulin genes to produce specifically mutated genes expressing altered antibodies. 4. The study of immunodeterminants of bacteria causing significant diseases on a global scale, so as to evaluate procedures for vaccine development. We have determined the specific interaction between microbial polysaccharides such as dextran and a number of monoclonal antibodies in the past. We have prepared many complex fragments of the capsular polysaccharide of Shigella dysenteriae type 1 by sophisticated syntheses, and have mapped the binding area of a monoclonal antibody towards this disease-causing micro-organism. In this manner, the immuno-determinant of this polysaccharide could be defined. Both the variable region of the heavy (VH) and the light (VL) chains have been cloned and sequenced, and they have been incorporated in a bacterial expression vector. The VH and VL are linked by a short DNA sequence coding for a fifteen amino acid peptide so that the expressed protein is a covalently linked FV. Expression is presently going on in E. coli.